Background: MOH (medication overuse headache) is regarded as a complication of chronic migraines (CMs), with a general acknowledgment of reciprocal triggering between these two conditions. The present study aims to investigate the clinical parameters of relevance for the development of MOH among patients with CM, as well as for the subtype classification of MOHs. Method: We compared two groups of CM patients, with and without MOH, separated based on their demographic data and migraine characteristics. A subgroup of MOH accompanied by psychiatric co-morbidities (depression, anxiety, sleep disorder) was delineated, and the clinical features of relevance for the progression of MOH into the complicated state were evaluated. Results: The study revealed a higher prevalence of a family history of migraine in both the MOH and potentially complicated MOH subgroups (p < 0.001, p = 0.036), along with a higher prevalence of bilateral pain localization (p = 0.033, 0.021). Symptoms commonly associated with migraines, such as nausea, vomiting, photophobia, phonophobia, and osmophobia, were more common in both the MOH and potentially complicated MOH subgroups (p < 0.05). Furthermore, a positive correlation was found for the frequency (p < 0.001) and severity (p = 0.010) of migraine attacks and the duration of headaches (p = 0.007), atopy (p = 0.017), sleep disturbances (p = 0.011), and emotional stress (p = 0.022) in the MOH group. Conclusion: We found a positive correlation between the prevalence of MOH among patients with CM and a family history of migraines, higher frequency and intensity of headaches, bilateral manifestation, sleep disturbances, and emotional stress. Moreover, symptoms accompanying migraines were found to be more prevalent in individuals with MOH and potentially complicated MOH.

UNASSIGNED: Migraine has a negative impact on patients\' quality of life, with the frequency of attacks being associated with greater disability and poorer health status. Frequent migraine-type headaches require prophylactic treatment, which has so far been of limited effectiveness until advent of calcitonin gene-related peptide (CGRP) monoclonal antibody.
UNASSIGNED: A prospective analysis was conducted of data from 41 migraine patients who experienced 4 or more monthly migraine days (MMD) longer than three months. At the beginning of the study, treatment with monoclonal antibodies against CGRP (fremanezumab 225 mg or erenumab 70 or 140 g per month) was prescribed according to the indications. The effect of the medications was evaluated after 3-month period.
UNASSIGNED: The mean age of patients was 37.17 (±11.78) years. It was found that 17 patients (41.5%) had episodic migraine (EM) and 24 (58.5%) had chronic migraine (CM). Fremanezumab was prescribed to 26 patients (63.4%) and erenumab to 15 patients (36.6%); among the latter, 13 patients used 70 mg/month and 2 patients used 140 mg/month. Three months after treatment, CM changed to EM for 19 patients (79.2%), 27 patients (65.9%) had ≥50% reduction in the number of MMD and total migraine disability assessment (MIDAS) score was reduced by >50% in 31 patients (75.6%). Also, all areas of quality of life of patients were improved after 3 months continued treatment compared to baseline.
UNASSIGNED: For more than half the patients using fremanezumab or erenumab after 3-month period, MMD decreased by ≥50% and total MIDAS score by >50 points. All areas of quality of life were improved after prophylactic treatment of migraine.
UNASSIGNED: Migrena neigiamai veikia pacientų gyvenimo kokybę ir galvos skausmų dažnis yra susijęs su didesnia negalia ir blogesne sveikata. Esant dažnam migreniam galvos skausmui yra reikalingas profilaktinis gydymas, kurio efektyvumas, iki atsirandant biologinei terapijai, buvo ribotas.
UNASSIGNED: Perspektyviniame tyrime dalyvavo 41 migrena sergantys pacientai, kuriems pasireiškė 4 ir daugiau migreninių dienų per mėnesį (MDM) ilgiau kaip 3 mėnesius. Pacientams paskirti su kalcitonino genu susijusį baltymą ir jo receptorius veikiantys (angl. calcitonin gene-related peptide, CGRP) monokloniniai antikūnai (fremanezumabas 225 mg ar erenumabas 70 mg ar 140 mg per mėnesį). Gydymo efektyvumas įvertintas po 3 mėnesių.
UNASSIGNED: Pacientų amžiaus vidurkis buvo 37,17 (±11,78) metų. Nustatyta, kad epizodinę migreną (EM) turėjo 17 (41,5 proc.) pacientų, o lėtinę migreną (LM) – 24 (58,5 proc.) pacientai. Fremanezumabas paskirtas 26 (63,4 proc.), o erenumabas – 15 (36,6 proc.) pacientams; atitinkamai, 13 pacientų naudojo erenumabo 70 mg per mėnesį, o 2 pacientai – 140 mg per mėnesį. Po trijų mėnesių vartojant monokloninius antikūnus, LM pasikeitė į EM 19 (79,2 proc.) pacientų, ≥50 proc. MDM sumažėjo 27 (65,9 proc.) pacientams ir 31 (75,6 proc.) pacientui bendras migrenos įtakos veiklai (angl. migraine disability assessment scale, MIDAS) balas sumažėjo >50 proc. Visose srityse gyvenimo kokybės įvertinimas pagerėjo 3 mėnesius skiriant monokloninius antikūnus.
UNASSIGNED: Daugiau kaip pusei pacientų sumažėjo ≥50 proc. MDM ir >50 proc. MIDAS balai, gyvenimo kokybės įvertinimas visose srityse pagerėjo po 3 mėnesių skiriant gydymą monokloniniais antikūnais.

BACKGROUND: Alpha 7 nicotinic acetylcholine receptor (α7nAChR)-mediated astrocytic activation is closely related to central sensitization of chronic migraine (CM). Xiongzhi Dilong decoction (XZDL), originated from Xiongzhi Shigao decoction of Yi-zong-jin-jian, has been confirmed to relieve CM in experiment and clinic. However, its underlying mechanism for treating CM has not been elucidated.
OBJECTIVE: To reveal the underlying mechanisms of XZDL to alleviate CM in vivo focusing mainly on α7nAChR-mediated astrocytic activation and central sensitization in TNC.
METHODS: CM rat model was established by subcutaneous injection of nitroglycerin (NTG) recurrently, and treated with XZDL simultaneously. Migraine-like behaviors of rats (ear redness, head scratching, and cage climbing) and pain-related reactions (mechanical hind-paw withdrawal threshold) of rats were evaluated before and after NTG injection and XZDL administration at different points in time for nine days. The immunofluorescence single and double staining were applied to detect the levels of CGRP, c-Fos, GFAP and α7nAChR in NTG-induced CM rats. ELISA kits were employed to quantify levels of TNF-α, IL-1β, and IL-6 in medulla oblongata of CM rats. The expression levels of target proteins were examined using western blotting. Finally, methyllycaconitine citrate (MLA, a specific antagonist of α7nAChR) was applied to further validate the mechanisms of XZDL in vivo.
RESULTS: XZDL significantly attenuated the pain-related behaviors of the NTG-induced CM rats, manifesting as constraints of aberrant migraine-like behaviors including elongated latency of ear redness and decreased numbers of head scratching and cage climbing, and increment of mechanical withdrawal threshold. Moreover, XZDL markedly lowered levels of CGRP and c-Fos, as well as inflammatory cytokines (IL-1β, IL-6 and TNF-α) in CM rats. Furthermore, XZDL significantly enhanced α7nAChR expression and its co-localization with GFAP, while markedly inhibited the expression of GFAP and the activation of JAK2/STAT3/NF-κB pathway in the TNC of CM rats. Finally, blocking α7nAChR with MLA reversed the effects of XZDL on astrocytic activation, central sensitization, and the pain-related behaviors in vivo.
CONCLUSIONS: XZDL inhibited astrocytic activation and central sensitization in NTG-induced CM rats by facilitating α7nAChR expression and suppressing JAK2/STAT3/NF-κB pathway, implying that the regulation of α7nAChR-mediated astrocytic activation represents a novel mechanism of XZDL for relieving CM.

BACKGROUND: High-frequency headache/migraine (HFM) and overuse of acute medication (medication overuse [MO]) are associated with increased disability and impact. Experiencing both HFM and MO can potentially compound impacts, including stigma; however, evidence of this is limited. The objective of this report was to evaluate self-reported stigma, health-related quality of life (HRQoL), disability, and migraine symptomology in US adults with HFM + MO from the Harris Poll Migraine Report Card survey.
METHODS: US adults (≥ 18 yrs., no upper age limit) who screened positive for migraine per the ID Migraine™ screener completed an online survey. Participants were classified into \"current HFM + MO\" (≥ 8 days/month with headache/migraine and ≥ 10 days/month of acute medication use over last few months) or \"previous HFM + MO\" (previously experienced HFM + MO, headaches now occur ≤ 7 days/month with ≤ 9 days/month of acute medication use). Stigma, HRQoL, disability, and most bothersome symptom (MBS) were captured. The validated 8-item Stigma Scale for Chronic Illnesses (SSCI-8) assessed internal and external stigma (scores ≥ 60 are clinically significant). Raw data were weighted to the US adult population. Statistically significant differences were determined by a standard t-test of column proportions and means at the 90% (p < 0.1) and 95% (p < 0.05) confidence levels.
RESULTS: Participants (N = 550) were categorized as having current (n = 440; mean age 41.1 years; 54% female; 57% White, not Hispanic; 24% Hispanic; 11% Black, not Hispanic) or previous (n = 110; mean age 47.2 years; 49% female; 75% White, not Hispanic; 13% Hispanic; 4% Black, not Hispanic) HFM + MO. Compared to those with previous HFM + MO (21%), adults with current HFM + MO were more likely to experience clinically significant levels of stigma (47%). Men with current HFM + MO (52% compared to men with previous HFM + MO [25%] and women with current [41%] or previous [18%] HFM + MO), non-Hispanic Black (51% compared to White, not Hispanic [45%] and Hispanic [48%] current HFM + MO groups and White, not Hispanic previous HFM + MO [12%]), current HFM + MO aged 18-49 years (50% compared to those with current HFM + MO aged ≥ 50 years [33%] and those with previous HFM + MO aged 18-49 [34%] and ≥ 50 years [4%]), and employed respondents (53% current and 29% previous compared to those not employed [32% current and 12% previous]) reported higher rates of clinically significant stigma. Those with current HFM + MO were more likely to have worse HRQoL and disability due to headache/migraine. Respondents aged ≥ 50 years with current HFM + MO were more likely than respondents aged 18-49 years with current HFM + MO to indicate that their overall quality of life (66% vs. 52%) and their ability to participate in hobbies/activities they enjoy were negatively impacted by headache/migraine (61% vs. 49%). Pain-related symptoms were identified as the MBS.
CONCLUSIONS: Together these data suggest that current and previous HFM + MO can be associated with undesirable outcomes, including stigma and reduced HRQoL, which were greatest among people with current HFM + MO, but still considerable for people with previous HFM + MO.

BACKGROUND: Management of patients with migraine who have concomitant medication overuse (MO) or medication overuse headache (MOH) is a major problem in clinical practice. Detoxification of acute analgesics before or during initiation of prophylactic therapy has long been recommended although this concept has recently been questioned. Additionally, relapse after detoxification is a common problem. This real-world study analyses the initial and sustained effectiveness of prophylactic migraine therapy with CGRP (receptor) antibodies without prior detoxification in patients with comorbid MO or MOH for up to one year.
METHODS: A retrospective real-world analysis was performed on 291 patients (episodic migraine (EM) with MO (EM-MO; n = 35), EM without MO (EM-noMO; n = 77), chronic migraine (CM) with MOH (CM-MOH; n = 109), CM without MOH (CM-noMOH; n = 70). All patients began treatment with either erenumab (n = 173), fremanezumab (n = 70) or galcanezumab (n = 48) without prior detoxification. Data were available for up to 12 months of treatment. Responder rates for monthly headache days (MHD), monthly migraine days (MMD) and monthly acute medication intake (AMD) were analysed.
RESULTS: All groups showed a significant reduction in MHD, MMD and AMD at the last observed time point compared to baseline. In patients with CM and MOH, 60.6% (66/109) no longer fulfilled the definition of MO or MOH and a further 13.8% (15/109) had only EM-MO. In the EM cohort, 89% (31/35) of MO patients lost their MO during therapy. MHD and AMD 30% responder rates were comparable for CM-MOH and CM-noMOH (MHD: CM-MOH: 56.0% vs. CM-noMOH: 41.4%, p = 0.058, AMD: CM-MOH: 66.1% vs. CM-noMOH: 52.9%, p = 0.077). MMD responder rate did not differ significantly (after Bonferroni adjustment) (CM-MOH: 62.4% vs. CM-noMOH: 47.1%, p = 0.045, α = 0.017). After successful initiation of therapy, 15.4% of the initial CM-MOH patients relapsed and met the criterion for CM-MOH at the end of follow-up. There were no antibody specific differences in response to therapy.
CONCLUSIONS: Our data confirms the effectiveness of CGRP antibody treatment in migraine patients with additional MOH or MO in a real-world setting. Low relapse rates after initial successful therapy support an early start of CGRP antibody treatment in patients with MOH or MO.
BACKGROUND: No registration, retrospective analysis.

UNASSIGNED: This real-world study aimed to investigate how onabotulinumtoxinA affects the outcome of migraine, along with accompanying anxiety, depression, and bruxism among a group of patients with chronic migraine (CM) and define predictors of good response.
UNASSIGNED: Patients diagnosed with CM who received onabotulinumtoxinA were included in this single-center, real-world retrospective cohort study. Monthly headache days (MHDs), monthly migraine days (MMDs), headache intensity (numeric rating scale-NRS) and headache characteristics were evaluated at baseline and 12 weeks post-treatment. Patient-reported outcome measures (PROMs) included Migraine Disability Assessment Scale (MIDAS), Headache Impact Test-6 (HIT-6) scores, 12-item Allodynia Symptom Checklist (ASC-12), Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI). Response to onabotulinumtoxinA (% reduction in MHDs) and treatment-related adverse events (TRAEs) were also evaluated. OnabotulinumA was applied to the masseter muscles in patients complaining of bruxism.
UNASSIGNED: A total of 72 patients (mean ± SD age: 36.3 ± 8.5 years; 91.7% were female) diagnosed with CM were included. OnabotulinumtoxinA revealed significant decrease in median (IQR) MHDs [from 20(15-25) at baseline to 6(4-10), p < 0.001], MMDs [from 9(6-12) to 3(1-6), p < 0.001] and NRS [from 9(8-10) to 7(6-8), p < 0.001], and the MIDAS [from 54(30-81) to 16(7-24), p < 0.001], HIT-6 [from 67(65-69) to 58(54-64), p < 0.001], ASC-12 [from 6(1.5-9) to 2(0-9), p = 0.002], BAI [from 12(6.5-19) to 9(3-17), p < 0.001] and BDI [from 11(6.5-17) to 3(2-7) p < 0.001] scores at 12 weeks post-treatment. Patients complaining of bruxism received onabotulinumtoxinA injections in the first n = 27 (37.5%) and 12. week post-treatment n = 19 (70.4%) periods. Overall, 70.8% of patients responded (≥50% reduction in MHDs), while 29.2% did not (<50% reduction). Both groups showed similar characteristics in demographics, migraine history, baseline PROMs scores, comorbidities, and prior treatments.
UNASSIGNED: OnabotulinumtoxinA is an effective treatment option that rapidly improves migraine outcomes, disability, and impact while also alleviating comorbid depression and/or anxiety. This study\'s noteworthy finding is that onabotulinumtoxinA is effective in a majority of CM patients, irrespective of their prior treatment history, migraine characteristics, or concurrent comorbidities. Furthermore, we identified no specific predictors for a favorable response to onabotulinumtoxinA. Applying onabotulinumtoxinA to the masseter muscles can relieve discomfort associated with concurrent bruxism; however, it does not impact migraine outcomes.

OBJECTIVE: Chronic migraine is a disabling progressive disorder without effective management approaches. Animal models have been developed and used in chronic migraine research. However, there are several problems with existing models. Therefore, we aimed to summarize and analyze existing animal models to facilitate translation from basic to clinical.
RESULTS: The most commonly used models are the inflammatory soup induction model and the nitric oxide donor induction model. In addition, KATP openers have also been used in model induction. Based on the above models, some molecular targets have been identified, such as glutamate receptors. However, each model has its shortcomings and characteristics, and there are still some common problems that need to be solved, such as spontaneous headache, evaluation criteria after model establishment, and identification methods. In this review, we summarized and highlighted the advantages and limitations of the currently commonly used animal models of chronic migraine with a special focus on drug discovery and current therapeutic strategies, and discussed the directions that can be worked on in the future.

UNASSIGNED: Real-world studies have shown the sustained therapeutic effect and favourable safety profile of OnabotulinumtoxinA (BoNTA) in the long term and up to 4 years of treatment in chronic migraine (CM). This study aims to assess the safety profile and efficacy of BoNTA in CM after 5 years of treatment in a real-life setting.
UNASSIGNED: We performed a retrospective chart review of patients with CM in relation to BoNTA treatment for more than 5 years in 19 Spanish headache clinics. We excluded patients who discontinued treatment due to lack of efficacy or poor tolerability.
UNASSIGNED: 489 patients were included [mean age 49, 82.8% women]. The mean age of onset of migraine was 21.8 years; patients had CM with a mean of 6.4 years (20.8% fulfilled the aura criteria). At baseline, patients reported a mean of 24.7 monthly headache days (MHDs) and 15.7 monthly migraine days (MMDs). In relation to effectiveness, the responder rate was 59.1% and the mean reduction in MMDs was 9.4 days (15.7 to 6.3 days; p < 0.001). The MHDs were also reduced by 14.9 days (24.7 to 9.8 days; p < 0.001). Regarding the side effects, 17.5% experienced neck pain, 17.3% headache, 8.5% eyelid ptosis, 7.5% temporal muscle atrophy and 3.2% trapezius muscle atrophy. Furthermore, after longer-term exposure exceeding 5 years, there were no serious adverse events (AE) or treatment discontinuation because of safety or tolerability issues.
UNASSIGNED: Treatment with BoNTA led to sustained reductions in migraine frequency, even after long-term exposure exceeding 5 years, with no evidence of new safety concerns.

OBJECTIVE: To evaluate the effectiveness of a multidisciplinary program, including Cognitive behavioral therapy (CBT), in the treatment of patients with chronic migraine (CM) and concomitant chronic insomnia (CI).
METHODS: The study included 96 patients with CM and CI, average age 35.7±8.6. All patients underwent clinical interviews and testing using clinical and psychological techniques. Patients were randomized into two groups: group 1 received study treatment (an multudisciplinary program including CBT for pain and insomnia, combined with standard treatment for migraine), group 2 received standard treatment for migraine (preventive and acute pharmacotherapy for migraine, recommendations about lifestyle and sleep hygiene). All patients were assessed for clinical and psychological parameters before treatment and at 3, 6, 12 and 18 months follow-up.
RESULTS: At 3 month follow-up a statistically significant improvement was observed in group 1: a decrease in the frequency of headaches and the use of painkillers, parameters on the Insomnia Severity Index (ITI), the State-Trait Anxiety Inventory (STAI), the Beck Depression Inventory, and the Migraine Disability Assessment (MIDAS) (p<0.05). At 6, 12 and 18 months follow-up the achieved improvements were maintained. At 3 month follow-up, group 2 showed a statistically significant improvement in only 4 parameters: a decrease in the frequency of headaches and painkiller use, and parameters for ITI and MIDAS. These parameters increased to values that were not statistically significantly different from the parameters before treatment in group 2 at 6 month follow-up. At 3 month follow-up in group 165% of patients achieved clinical effect (CE) according to CM (headache frequency decreased by 50% or more), in group 2 - 40%, which was not statistically significantly different (p>0.001); in group 1, 76% of patients achieved CE according to CI (ITI decreased by 8 points or more), which is statistically significantly more than in group 2 with 45% of patients with CE (p<0.001). At 18 month follow-up, in group 1, 81.5% of patients achieved CE according to CM, which is statistically significantly more than in group 2 with 33% of patients with CE (p<0.001); in group 1, 85% of patients achieved CE according to CI, which is statistically significantly more than in group 2, where 38% of patients had CE (p<0.001).
CONCLUSIONS: High effectiveness of CBT in patients with CM and combined CI was noted.
UNASSIGNED: Оценить эффективность междисциплинарной программы, включающей когнитивно-поведенческую терапию (КПТ), в лечении пациентов с хронической мигренью (ХМ) и сочетанной хронической инсомнией (ХИ).
UNASSIGNED: В исследование включены 96 пациентов с ХМ и ХИ, средний возраст 35,7±8,6 года. Со всеми пациентами проводились клиническая беседа и тестирование с помощью клинико-психологических методик. Пациенты были рандомизированы в две группы: 1-я группа получала стандартное лечение (фармакотерапию профилактическую и для купирования мигрени, рекомендации по образу жизни и гигиене сна) и КПТ, 2-я группа — только стандартное лечение. У всех пациентов оценивались клинико-психологические показатели до лечения и на 3, 6, 12 и 18-й месяцы после лечения.
UNASSIGNED: Через 3 мес терапии в 1-й группе наблюдалось статистически значимое улучшение: снижение частоты приступов головной боли и приема обезболивающих, показателей по Индексу тяжести инсомнии (ИТИ), шкале личностной и ситуативной тревоги Спилбергера—Ханина, шкале депрессии Бека, шкале оценки влияния мигрени на повседневную активность (ШОВМА) (p<0,05). Через 6, 12 и 18 мес терапии достигнутые улучшения сохранились. Через 3 мес терапии во 2-й группе наблюдалось статистически значимое (p<0,05) улучшение только по 4 параметрам: снижение частоты приступов головной боли и приема обезболивающих, показателей по ИТИ и ШОВМА. С 6 мес терапии во 2-й группе эти показатели статистически значимо не отличались от показателей до лечения. Через 3 мес терапии клинического эффекта (КЭ) по ХМ (снижение частоты головной боли на 50% и более) в 1-й группе достигли 65% пациентов, во 2-й группе — 40%; КЭ по ХИ (ИТИ уменьшился на 8 баллов и более) в 1-й группе — 76% пациентов, во 2-й группе — 45% (p<0,001). Через 18 мес терапии КЭ по ХМ в 1-й группе достигли 81,5% пациентов, во 2-й группе — 33% (p<0,001); КЭ по ХИ в 1-й группе — 85% пациентов, во 2-й группе — 38% (p<0,001).
UNASSIGNED: Отмечена высокая эффективность КПТ у пациентов с ХМ и сочетанной ХИ.

OBJECTIVE: To describe the association between day-to-day peak pain severity and clinical factors in individuals with chronic migraine (CM).
BACKGROUND: Little is known about how clinical factors relate to day-to-day pain severity in individuals with CM.
METHODS: Adults with CM were enrolled into this observational prospective cohort study that collected daily data about headache, associated symptoms, and lifestyle factors using a digital health platform (N1-Headache™) for 90 days. \"Migraine days\" were defined as days in which a headache occurred that had features described by the International Classification of Headache Disorders criteria. On these days, peak pain severity was recorded on a 4-point scale; on non-headache days peak pain severity was imputed as \"0/none\". The associations between peak pain severity and 12 clinical factors were modeled and adjusted for sex, age, daily headache, presence of menstrual bleeding, day of the week, and disability. All numerical and Likert scale variables were standardized prior to analysis.
RESULTS: Data were available for 392 participants (35,280 tracked days). The sample was predominantly female (90.6%), with a mean (standard deviation) age of 39.9 (12.8) years. In the final multivariable model with random intercept and slopes, higher than typical self-reported levels of standardized stress (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.04-1.11), standardized irritability (OR 1.05, 95% CI 1.02-1.08), standardized sadness (OR 1.05, 95% CI 1.02-1.07), fatigue (OR 1.25, 95% CI 1.15-1.36), eyestrain (OR 1.38, 95% CI 1.26-1.52), neck pain (OR 1.94, 95% CI 1.76-2.13), skin sensitivity (OR 1.61, 95% CI 1.44-1.80), and dehydration (OR 1.29, 95% CI 1.18-1.42) were associated with higher reported peak pain severity levels, while standardized sleep quality (OR 0.96, 95% CI 0.93-0.99) and standardized waking feeling refreshed (OR 0.84, 95% CI 0.81-0.88) were associated with lower reported peak pain severity levels. The inclusion of a random intercept and random slopes improved upon more parsimonious models and illustrated large differences in individuals\' reporting of peak severity according to the levels of the associated clinical factors.
CONCLUSIONS: Our data showed that the experience of CM, from a pain severity perspective, is complex, related to multiple clinical variables, and highly individualized. These results suggest that future work should aim to study a personalized approach to both medical and behavioral interventions for CM based on which clinical factors relate to the individual\'s experience of pain severity.